Non-Small Cell Lung Cancer
Conditions
Brief summary
This is a first-in-human (FIH), multicenter, non-randomized, openlabel, phase 1 study of ABSK112 in patients with NSCLC to evaluate the safety, tolerability, PK, and preliminary antitumor efficacy.
Detailed description
The study will be started with a dose escalation part of ABSK112 administered in repeated 28-day cycles in patients with NSCLC. The expansion part of oral ABSK112 at the recommended dose of expansion (RDE) will be followed to evaluate safety, tolerability, and preliminary antitumor activity among patients with locally advanced or metastatic NSCLC harboring EGFR Exon20ins.
Interventions
DRUGABSK112
In the escalation part, patients will receive a single dose of oral ABSK112 on Cycle1 Day1 only, and then patients will continuously receive ABSK112 once daily (QD) or twice daily (BID) in subsequent cycles. In the expansion part, patients will each be treated at the selected RDE dose level.
Sponsors
Abbisko Therapeutics Co, Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients should understand, sign, and date the written informed consent form prior to screening. 2. Male or female aged 18 years or older. 3. Patients with histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC. 4. Cohort-specific inclusion criteria: 1. For the escalation part (except for the RDE confirmation part), patients have progressed on, rejected, or are intolerant of standard therapy, or for whom no standard therapy exists 2. For RDE confirmation in the escalation part: same as Cohort 1 in the expansion part 3. For the expansion part, patients have documented EGFR in-frame exon 20 insertion mutations confirmed by certificated local laboratories; and must also meet all criteria for the cohort in which their entry is proposed. 5. Patients must have at least one measurable target lesion according to RECIST v1.1 6. ECOG performance status 0 or 1 7. 7\. Life expectancy ≥3 months 8. Adequate organ function and bone marrow function. 9. Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130 mmol/L, potassium within institutional normal limits 10. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle1 Day1. 11. For patients participating in food effect exploration part: 1. Be able to eat a standardized high-fat meal within 30 minutes 2. Be able to fast for 10 hours. 12. Non-surgically sterilized male or female patients of childbearing potential must agree to use highly effective methods of birth control during the study treatment and for approximately 6 months after the last dose of study drug. A condom is also required to be used by vasectomized men to prevent delivery of the drug via seminal fluid.
Exclusion criteria
1. Known allergy or hypersensitivity to any component of the investigational product. 2. NSCLC patients with EGFR Cys797Ser (C797S) mutation. 3. Cohort-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of DLT | from Day1 to Day28 | Dose-limiting toxicities |
| AEs | The date of signing the informed consent form until 30 days (including Day 30) after the last dose of study drug, assessed up to 50 months. | Adverse events |
| AESIs | The date of signing the informed consent form until 30 days (including Day 30) after the last dose of study drug, assessed up to 50 months. | Adverse events of special interest (AESIs) |
| SAEs | The date of signing the informed consent form until 30 days (including Day 30) after the last dose of study drug, assessed up to 50 months. | Serious adverse events (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CL/F | From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months | apparent oral clearance |
| Cmax,ss | From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months | maximum observed concentration after multiple doses |
| Cmin,ss | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | minimum observed concentration after multiple doses |
| AUCtau,ss | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | area under the concentration-time curve after multiple doses |
| AR | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | accumulation ratio |
| Cmax | From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months | Maximum observed concentration |
| ORR | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | Objective response rate |
| DOR | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | Duration of response |
| PFS | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | Progression-free survival |
| DCR | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | Disease control rate |
| OS | From date of enrollment（Day1）until the date of death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 100 months. | Overall survival |
| tmax | From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months. | time to maximum observed concentration |
| AUC | From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months | area under the concentration-time curve |
| t1/2 | From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months | elimination half-life |
| Vz/F | From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months | apparent volume of distribution |
Countries
China, United States
Contacts
Primary ContactYuan Lu
Backup ContactYinan Lin
Outcome results
None listed